Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Acta Biomater. 2015 Apr;17:16-25. doi: 10.1016/j.actbio.2015.01.031. Epub 2015 Jan 30.
Hydroxyapatite (HA) reinforced collagen scaffolds have shown promise for synthetic bone graft substitutes and tissue engineering scaffolds. Freeze-dried HA-collagen scaffolds are readily fabricated and have exhibited osteogenicity in vivo, but are limited by an inherent scaffold architecture that results in a relatively small pore size and weak mechanical properties. In order to overcome these limitations, HA-collagen scaffolds were prepared by compression molding HA reinforcements and paraffin microspheres within a suspension of concentrated collagen fibrils (∼ 180 mg/mL), cross-linking the collagen matrix, and leaching the paraffin porogen. HA-collagen scaffolds exhibited an architecture with high porosity (85-90%), interconnected pores ∼ 300-400 μm in size, and struts ∼ 3-100 μm in thickness containing 0-80 vol% HA whisker or powder reinforcements. HA reinforcement enabled a compressive modulus of up to ∼ 1 MPa, which was an order of magnitude greater than unreinforced collagen scaffolds. The compressive modulus was also at least one order of magnitude greater than comparable freeze-dried HA-collagen scaffolds and two orders of magnitude greater than absorbable collagen sponges used clinically. Moreover, scaffolds reinforced with up to 60 vol% HA exhibited fully recoverable elastic deformation upon loading to 50% compressive strain for at least 100,000 cycles. Thus, the scaffold mechanical properties were well-suited for surgical handling, fixation, and bearing osteogenic loads during bone regeneration. The scaffold architecture, permeability, and composition were shown to be conducive to the infiltration and differentiation of adipose-derive stromal cells in vitro. Acellular scaffolds were demonstrated to induce angiogenesis and osteogenesis after subcutaneous ectopic implantation by recruiting endogenous cell populations, suggesting that the scaffolds were osteoinductive.
羟基磷灰石（HA）增强胶原支架已被证明在合成骨移植物替代物和组织工程支架方面具有潜力。冻干的 HA-胶原支架易于制备，并在体内表现出成骨性，但由于固有支架结构导致相对较小的孔径和较弱的机械性能而受到限制。为了克服这些限制，通过在浓缩胶原纤维（约 180mg/mL）悬浮液中压缩成型 HA 增强剂和石蜡微球，交联胶原基质并提取石蜡致孔剂，制备了 HA-胶原支架。HA-胶原支架具有高孔隙率（85-90%）、相互连接的孔径约为 300-400μm、厚度为 3-100μm 的支柱的结构，其中含有 0-80vol%HA 晶须或粉末增强剂。HA 增强剂使压缩模量高达约 1MPa，比未增强的胶原支架高一个数量级。压缩模量也至少比可比的冻干 HA-胶原支架高一个数量级，比临床上使用的可吸收胶原海绵高两个数量级。此外，用高达 60vol%HA 增强的支架在负载至 50%压缩应变时表现出完全可恢复的弹性变形，至少 100,000 次循环。因此，支架的机械性能非常适合手术处理、固定和在骨再生过程中承受成骨负荷。支架的结构、渗透性和组成有利于脂肪来源基质细胞在体外的渗透和分化。非细胞支架通过募集内源性细胞群在皮下异位植入后被证明可诱导血管生成和成骨，表明支架具有骨诱导性。
